This proposal is designed to initiate studies elucidating the biologic significance of ovine placental cortisol biosynthesis by examining its ontogenesis and regulation in vitro and by testing the in vitro findings in vivo. The hypotheses to be tested are: that placental cortisol biosynthesis is highest at mid-gestation; that its major precursors are progesterone and pregnenolone sulfate; and that placental cortisol biosynthesis is hormonally regulated. Fresh placental tissue, obtained at four stages of gestation, will be incubated with tritiated precursors to examine ontogenesis and precursor product relationships in vitro. Similar incubations will be done to examine multiple potential modulators (ACTH, prolactin, prostaglandins, and steroids) and to determine dose-response. Active modulators will be infused into either the uterine or fetal circulations of chronically catheterized animals and their effects assessed in vivo by examining the conversion of labeled precursor to cortisol in placental venous effluent. In the initial experiments, results will be correlated with the endocrine responsivity of the fetal adrenals. Placental cortisol biosynthetic capability is a new finding. It warrants further investigation because of its basic biologic significance as a potential modulator of gestational events other than the initiation of labor, and as a source of fetal cortisol during mid-gestation.